Why a Common Treatment Fails

The new findings show that the androgen receptor, through which male hormones like testosterone work, is much more versatile than previously thought. Under certain conditions the molecule spurs growth, and at other times the molecule squelches growth.

The new findings raise the possibility that under some conditions, some treatments designed to treat prostate cancer could instead remove one of the body's natural brakes on the spread of the disease in the body. The researchers stress that the results are based on laboratory studies analysing human prostate cancer cells in culture and on findings in mice, and it is too soon to know yet whether the findings apply directly to prostate cancer in men.

With hormone therapy, physicians blunt the effects of male hormones like testosterone to bring the disease in the prostate to a halt. One form of hormone therapy works by blocking the androgen receptor. The research team found that blocking the receptor indeed prevents some cells in the prostate from growing, just as scientists expected. But the scientists unexpectedly found that blocking the receptor actually spurs other prostate cells to grow. The androgen receptor acts differently in different cells in prostate tissue, the researchers say.

The team found that, as expected, the androgen receptor in prostate support cells known as stromal cells stimulates growth of cells, including cancer cells, in the prostate. It was also found, surprisingly, that the receptor actually acts as a tumour suppressor in epithelial cells known as basal cells in the prostate.

Then the scientists knocked out the androgen receptor in specific sets of prostate cells and studied the results. As expected, when the molecule is turned off in stromal cells, growth of cancer cells in the prostate slows. But when the molecule is turned off in the epithelial cells, it removes one of the body's natural inhibitors that prevents prostate cancer cells from spreading, making cells more likely to invade other tissues.